Inici
Publicacions
Deciphering the Role of Histone Modifications in Uterine Leiomyoma: Acetylation of H3K27 Regulates the Expression of Genes Involved in Proliferation, Cell Signaling, Cell Transport, Angiogenesis and Extracellular Matrix Formation.

Deciphering the Role of Histone Modifications in Uterine Leiomyoma: Acetylation of H3K27 Regulates the Expression of Genes Involved in Proliferation, Cell Signaling, Cell Transport, Angiogenesis and Extracellular Matrix Formation.

Data de publicació: 30/05/2022 Data Ahead of Print: 30/05/2022

Autors de IIS La Fe

Maria Cristina Carbajo García

Autor
Lucia De Miguel Gómez

Autor
Elena Juarez Barber

Autor
Javier Monleón Sancho

Autor
Antonio Pellicer Martínez

Autor
Hortensia Ferrero Chafer

Autor

Autors aliens a IIS La Fe

Trelis, Alexandra
Flanagan, James M.

Grups d'Investigació

Biología Reproductiva y Bioingeniería en Reproducción Humana

Leader

Nicolás Garrido Puchalt
Medicina Reproductiva

Investigador Principal

José Morales Roselló

Abstract

Uterine leiomyoma (UL) is a benign tumor arising from myometrium (MM) with a high prevalence and unclear pathology. Histone modifications are altered in tumors, particularly via histone acetylation which is correlated with gene activation. To identify if the acetylation of H3K27 is involved in UL pathogenesis and if its reversion may be a therapeutic option, we performed a prospective study integrating RNA-seq (n = 48) and CHIP-seq for H3K27ac (n = 19) in UL vs MM tissue, together with qRT-PCR of SAHA-treated UL cells (n = 10). CHIP-seq showed lower levels of H3K27ac in UL versus MM (p-value < 2.2 x 10(-16)). From 922 DEGs found in UL vs. MM (FDR < 0.01), 482 presented H3K27ac. A differential acetylation (FDR < 0.05) was discovered in 82 of these genes (29 hyperacetylated/upregulated, 53 hypoacetylated/downregulated). Hyperacetylation/upregulation of oncogenes (NDP,HOXA13,COL24A1,IGFL3) and hypoacetylation/downregulation of tumor suppressor genes (CD40,GIMAP8,IL15,GPX3,DPT) altered the immune system, the metabolism, TGF beta 3 and the Wnt/beta-catenin pathway. Functional enrichment analysis revealed deregulation of proliferation, cell signaling, transport, angiogenesis and extracellular matrix. Inhibition of histone deacetylases by SAHA increased expression of hypoacetylated/downregulated genes in UL cells (p < 0.05). Conclusively, H3K27ac regulates genes involved in UL onset and maintenance. Histone deacetylation reversion upregulates the expression of tumor suppressor genes in UL cells, suggesting targeting histone modifications as a therapeutic approach for UL.

Dades de la publicació

ISSN/ISSNe:: 2227-9059, 2227-9059
Tipus:: Article
Pàgines:: -
DOI:: 10.3390/biomedicines10061279
PubMed:: 35740301
Factor d'Impacte:: 0,874 SCImago ℠
Quartil:: Q1 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Carbajo-Garcia, Maria Cristina:: Instituto de Investigación. Fundación IVI, IIS La Fe, 46026 Valencia, Spain

Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, 46010 Valencia, Spain

Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
de Miguel-Gomez, Lucia:: Instituto de Investigación. Fundación IVI, IIS La Fe, 46026 Valencia, Spain
Juarez-Barber, Elena:: Instituto de Investigación. Fundación IVI, IIS La Fe, 46026 Valencia, Spain
Trelis, Alexandra:: Hospital La Fe, 46009 Valencia, Spain
Monleon, Javier:: Hospital La Fe, 46009 Valencia, Spain
Pellicer, Antonio:: Instituto de Investigación. Fundación IVI, IIS La Fe, 46026 Valencia, Spain

IVIRMA Rome, 00197 Rome, Italy
Flanagan, James M.:: Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, UK
Ferrero, Hortensia:: Instituto de Investigación. Fundación IVI, IIS La Fe, 46026 Valencia, Spain